title: C1q-mediated chemotaxis by human neutrophils: involvement of gClqR and G-protein signalling mechanisms.
abstract: C1q, the first component of the classical pathway of the complement system, interacts with various cell types and triggers a variety of cell-specific cellular responses, such as oxidative burst, chemotaxis, phagocytosis, etc. Different biological responses are attributed to the interaction of C1q with more than one putative cell-surface C1q receptor/C1q-binding protein. Previously, it has been shown that C1q-mediated oxidative burst by neutrophils is not linked to G-protein-coupled fMet-Leu-Phe-mediated response. In the present study, we have investigated neutrophil migration brought about by C1q and tried to identify the signal-transduction pathways involved in the chemotactic response. We found that C1q stimulated neutrophil migration in a dose-dependent manner, primarily by enhancing chemotaxis (directed movement) rather than chemokinesis (random movement). This C1q-induced chemotaxis could be abolished by an inhibitor of G-proteins (pertussis toxin) and PtdIns(3,4,5)P3 kinase (wortmannin and LY294002). The collagen tail of C1q appeared to mediate chemotaxis. gC1qR, a C1q-binding protein, has recently been reported to participate in C1q-mediated chemotaxis of murine mast cells and human eosinophils. We observed that gC1qR enhanced binding of free C1q to adherent neutrophils and promoted C1q-mediated chemotaxis of neutrophils by nearly seven-fold. Our results suggests C1q-mediated chemotaxis involves gC1qR as well as G-protein-coupled signal-transduction mechanisms operating downstream to neutrophil chemotaxis.
authors.affiliation: MRC Immunochemistry Unit, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, U.K.
authors.forename: L E
authors.initials: LE
authors.lastname: Leigh
authors.forename: B
authors.initials: B
authors.lastname: Ghebrehiwet
authors.forename: T P
authors.initials: TP
authors.lastname: Perera
authors.forename: I N
authors.initials: IN
authors.lastname: Bird
authors.forename: P
authors.initials: P
authors.lastname: Strong
authors.forename: U
authors.initials: U
authors.lastname: Kishore
authors.forename: K B
authors.initials: KB
authors.lastname: Reid
authors.forename: P
authors.initials: P
authors.lastname: Eggleton
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D002352:Carrier Proteins; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D003094:Collagen / Q000737:chemistry; D015922:Complement C1q / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D009025:Morpholines / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D037342:Pertussis Toxin; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011951:Receptors, Complement / Q000502:physiology*; D015398:Signal Transduction; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; C087299:C1QBP protein, human; D002352:Carrier Proteins; D002867:Chromones; D004791:Enzyme Inhibitors; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011951:Receptors, Complement; D010566:Virulence Factors, Bordetella; C032402:complement 1q receptor; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D015922:Complement C1q; D003094:Collagen; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000077191:Wortmannin